Understanding the functional impact of genomic variants is one of the major goals of modern genetics and the underpinning of personalized medicine. To some extent, it is relatively easy to understand how non-synonymous protein coding variants exert their effects. Many synonymous and non-coding variants are known to act by altering the ef?ciency of pre-mRNA splicing. However, in most cases, it is exceedingly dif?cult to predict how these variants impact pre-mRNA splicing. Thus, a method that could simultaneously measure the splicing ef?ciency of thousands of exons and their variants would have a tremendous impact on the ?eld and our understanding of genome function. We propose to develop an assay we call Variant Exon analysis by Sequencing (VEX-Seq) that will facilitate the simultaneous analysis of the impact of intronic and exonic variants on the splicing of thousands of exons. This approach has the potential to have an extremely high impact on our understanding of genome function and how non-coding sequence variants impact pre-mRNA splicing.